Hajo Grundmann

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (153)848.66 Total impact

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    ABSTRACT: Objectives: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. Methods: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. Results: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. Conclusions: KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.
    No preview · Article · Jan 2016 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015.
    Full-text · Article · Dec 2015 · Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin
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    ABSTRACT: The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a UK MRSA database containing over 1,000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland and the Republic of Ireland over a decade. We sequenced 1,013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England, and otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualise MRSA outbreak investigations, and to detect the spread of resistance. The majority of isolates (n=783, 77%) belonged to CC22, which contains the dominant UK epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the UK and Ireland, and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.
    Full-text · Article · Dec 2015 · Genome Research
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    ABSTRACT: This study presents the first characterization of carbapenem-non-susceptible Klebsiella pneumoniae isolates by means of a structured six-month survey performed in Romania as part of an Europe-wide investigation. Klebsiella pneumoniae clinical isolates from different anatomical sites were tested for antibiotic susceptibility by phenotypic methods and confirmed by PCR for the presence of four carbapenemase genes. Genome macrorestriction fingerprinting with XbaI was used to analyze the relatedness of carbapenemase-producing Klebsiella pneumoniae isolates collected from eight hospitals. Among 75 non-susceptible isolates, 65 were carbapenemase producers. The most frequently identified genotype was OXA-48 (n = 51 isolates), eight isolates were positive for blaNDM-1 gene, four had the blaKPC-2 gene, whereas two were positive for blaVIM-1. The analysis of PFGE profiles of OXA-48 and NDM-1 producing K. pneumoniae suggests inter-hospitals and regional transmission of epidemic clones. This study presents the first description of K. pneumoniae strains harbouring blaKPC-2 and blaVIM-1 genes in Romania. The results of this study highlight the urgent need for the strengthening of hospital infection control measures in Romania in order to curb the further spread of the antibiotic resistance.
    Full-text · Article · Nov 2015 · PLoS ONE
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Extended-spectrum ß-lactamase producing Klebsiella pneumoniae have emerged as one of the major nosocomial pathogens. Between July and September 2012, a CTX-M-15 producing K. pneumoniae caused an outbreak in a university hospital in the Netherlands. The outbreak isolates were characterized and assigned to a novel sequence type (ST1427). An epidemiological link between affected patients was supported by patient contact tracing and whole-genome phylogenetic analysis. Genetic diversity was detected among multiple isolates obtained from different body sites of the index patient, which may relate to antibiotic treatment and/or host adaptation. Environmental contamination caused by the outbreak clone was found in the patient rooms even on medical equipment. The novel clone was not closely related to any known endemic/epidemic clone, but carried a set of a plasmid-borne resistance genes (blaCTX-M-15, blaTEM-1, blaOXA-1, aac(6')-Ib-cr, qnrB1, tetA(A), aac(3)-II). Analysis of its virulence factors revealed a previously uncharacterized capsular biosynthesis region and two uncharacterized fimbriae gene clusters, and suggested that the new clone was not hypervirulent. To our knowledge, this is the first outbreak report of K. pneumoniae ST1427, and our study could be of help to understand the features of this newly emerging clone.
    Full-text · Article · Oct 2015 · Frontiers in Microbiology
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    ABSTRACT: Extended-spectrum ß-lactamase producing Klebsiella pneumoniae have emerged as one of the major nosocomial pathogens. Between July and September 2012, a CTX-M-15 producing K. pneumoniae caused an outbreak in a university hospital in the Netherlands. The outbreak isolates were characterized and assigned to a novel sequence type (ST1427). An epidemiological link between affected patients was supported by patient contact tracing and whole-genome phylogenetic analysis. Genetic diversity was detected among multiple isolates obtained from different body sites of the index patient, which may relate to antibiotic treatment and/or host adaptation. Environmental contamination caused by the outbreak clone was found in the patient rooms even on medical equipment. The novel clone was not closely related to any known endemic/epidemic clone, but carried a set of a plasmid-borne resistance genes (blaCTX-M-15, blaTEM-1, blaOXA-1, aac(6')-Ib-cr, qnrB1, tetA(A), aac(3)-II). Analysis of its virulence factors revealed a previously uncharacterized capsular biosynthesis region and two uncharacterized fimbriae gene clusters, and suggested that the new clone was not hypervirulent. To our knowledge, this is the first outbreak report of K. pneumoniae ST1427, and our study could be of help to understand the features of this newly emerging clone.
    Full-text · Article · Oct 2015 · Frontiers in Microbiology

  • No preview · Article · Sep 2015 · Clinical Microbiology and Infection
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    K R Wilting · Y Stienstra · B Sinha · M Braks · D Cornish · H Grundmann
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    ABSTRACT: Two patients from Eritrea, recently arrived in the Netherlands, presented with fever and were investigated for malaria. Bloodfilms showed spirochetes but no blood parasites. Louse-borne relapsing fever caused by Borrelia recurrentis was diagnosed. Treatment was complicated by severe Jarisch–Herxheimer reactions in both patients. Physicians should be aware of the possibility of B. recurrentis infection in migrant populations who travel under crowded conditions, especially after passing through endemic areas such as Ethiopia and neighbouring countries. © 2015 European Centre for Disease Prevention and Control (ECDC). All rights reserved.
    Full-text · Article · Aug 2015 · Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin
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    ABSTRACT: The mec and bla systems, among other genetic factors, are critical in regulating the expression of methicillin resistance in Staphylococcus aureus. We examined by WGS a naturally occurring oxacillin-susceptible mecA-positive S. aureus isolate to identify the mechanism conferring oxacillin susceptibility. The mecA-positive oxacillin-susceptible S. aureus isolate GR2 (penicillin and oxacillin MICs 0.094 and 1 mg/L, respectively), belonging to clonal complex 80, was characterized. DNA fragment libraries were sequenced on Roche 454 and Illumina MiSeq sequencers and de novo assembly of the genome was generated using SeqMan NGen software. Plasmid curing was conducted by SDS treatment. Expression of mecA was quantified without/with β-lactam pressure. The genome of GR2 consisted of a 2 792 802 bp chromosome and plasmids pGR2A (28 895 bp) and pGR2B (2473 bp). GR2 carried SCCmec type IV, with a truncated/non-functional mecR1 gene and no mecI. A single copy of the bla system, with an organization unique for S. aureus, was found, harboured by plasmid pGR2A. Particularly, the blaZ gene was orientated like its regulatory genes, blaI and blaR1, and a gene encoding transposase IS66 was integrated between blaZ and the regulatory genes deleting the 5'-end of blaR1; blaI, encoding blaZ/mecA repressor, was intact. After plasmid loss, GR2 became penicillin and oxacillin resistant (MICs 0.5 and 6 mg/L, respectively). We can conclude that after exposure to β-lactams, the non-functional BlaR1 does not cleave the mecA repressor BlaI, derepression does not occur and mecA is not efficiently expressed. Removal of the bla system after curing of pGR2A allows constitutive expression of mecA, resulting in oxacillin and penicillin resistance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Full-text · Article · Jul 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Antibiotic resistance is a worldwide threat to health care as it impairs the effective treatment of bacterial infections. Measures against the spread of resistance are mainly focused on individual health care institutions as these are viewed as the main source of resistance. However, health care institutions are not completely independent in their control of the prevalence of resistance, as movement of patients between hospitals and care institutions can induce movement of resistant micro-organisms. In other words, antibiotic resistance follows the flow of patients. Mapping this flow of patients results in a network that includes all health care institutions, and has a distinctive modular structure. Patients are moved primarily within regions, much less so between regions. We argue that the structure of this health care network should be used to design efficient and effective control strategies. To this end, we advocate (a) regional coordination of control measures, (b) differentiation of investment in infection prevention according to the network position of the institution, and
    No preview · Article · Jun 2015 · Nederlands tijdschrift voor geneeskunde
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    T Van Der Kooi · H Boshuizen · S de Greeff · H Grundmann · W Zingg

    Preview · Article · Jun 2015
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    ABSTRACT: Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments.
    Full-text · Article · Mar 2015 · Scientific Reports
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    ABSTRACT: As MRSA are considered Staphylococcus aureus isolates with oxacillin minimum inhibitory concentration (MIC) of ≥4 mg/L or harboring the mecA gene. However, the presence of mecA does not necessarily lead to oxacillin resistance and mecA gene-carrying isolates may have oxacillin MIC within the susceptible range (≤2 mg/L). During the last few years it has become apparent that oxacillin-susceptible (OS) mecA-positive S. aureus isolates (commonly called OS-MRSA) are rather commonly detected worldwide and may remain undiagnosed using phenotypic susceptibility testing methods. This review will summarize the current reports on OS-MRSA isolations and the underlying mechanisms regulating the expression of oxacillin resistance and also oxacillin susceptibility in mecA-positive S. aureus isolates. As MRSA commonly cause severe infections against which effective therapies are limited, understanding of these mechanisms could enable the identification of new targets for the treatment or reversion of the MRSA phenotype.
    No preview · Article · Mar 2015 · Current pharmaceutical design
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    X Yan · Y Song · X Yu · X Tao · J Yan · F Luo · H Zhang · J Zhang · Q Li · L He · S Li · F Meng · H Grundmann
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    ABSTRACT: There is still limited knowledge about the prevalence and risk factors of nasal carriage for Staphylococcus aureus among healthy carriers in China. We investigated 2448 healthy adults (≥18 years of age) from Beijing (n = 1530) and Harbin (n = 918) by nasal screening. Participants were checked for carriage of S. aureus, and health-related and demographic information between 2009 and 2011 was gathered. A total of 403 S. aureus (403/2448, 16.5%) were recovered, 8 of which were methicillin resistant (8/2448, 0.33%). Three factors were independently associated with S. aureus nasal carriage: Harbin as city of residence (odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.41 to 2.85), age ≤24 years (OR = 1.77, 95% CI = 1.30-2.44) and non-Han ethnicity (OR = 1.58, 95% CI = 1.05 to 2.38). On the basis of population genetic analysis using multiple locus variable number of tandem repeats analysis (MLVA) and spa typing, MLVA complex (MC) 398 and MC5a were the most prevalent clonal lineages in this collection. In multivariate models, residing in Harbin (OR = 1.77, 95% CI = 1.07-2.92) and having household members in the healthcare profession (OR = 3.69, 95% CI = 1.14-11.92) were factors associated with carriage of clonal lineage MC398. On the other hand, female sex (OR = 3.15, 95% CI = 1.35-7.33) and a history of chronic liver disease (OR = 16.93, 95% CI = 2.91-98.59) were associated with the clonal lineage MC5a. The three most common spa types were t571 (10.9%), t189 (9.9%) and t701 (7.2%). These findings provide insight into the determinants of nasal carriage and ecology for some of the most successful strains of S. aureus among healthy people in Northern China. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Clinical Microbiology and Infection
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    ABSTRACT: The presence of the arginine catabolic mobile element (ACME) in Staphylococcus aureus has been reported to enhance the colonization of the human host. The aim of this study was to determine the genetic organization of composite islands harbouring ACME. Two ACME-positive S. aureus isolates obtained during two different surveys conducted in the Netherlands and Poland were characterized in this study. The isolates were analysed by spa typing, DNA microarrays and whole-genome sequencing. The two isolates harboured a truncated yet fully functional ACME type II with an identical nucleotide sequence, but differed in their adjacent mobile genetic elements. The first strain was a livestock-associated ST398-t011 MRSA, which had a staphylococcal cassette chromosome mec (SCCmec) composite island composed of SCCpls adjacent to orfX followed by ACME type II and SCCmec type IVa. The second ACME-positive isolate was an ST8-t008 MSSA. Its composite island showed an SCC-like element carrying the ccrC gene followed by ACME II. This is the first report of an ACME in a livestock-associated MRSA ST398. It is also the first presentation of an ACME composite island structure in an MSSA isolate. Our findings indicate an extensive mosaicism of composite islands in S. aureus, which has implications for the transmissibility among humans and thus for public health. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Jan 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Shiga toxin-producing Escherichia coli (STEC) O104:H4 emerged as an important pathogen when it caused a large outbreak in Germany in 2011. Little is known about the evolutionary history and genomic diversity of the bacterium. The current communication describes a comprehensive analysis of STEC O104:H4 genomes from the 2011 outbreak and other non-outbreak-related isolates. Outbreak-related isolates formed a tight cluster that shared a monophyletic relation with two non-outbreak clusters, suggesting that all three clusters originated from a common ancestor. Eight single nucleotide polymorphisms, seven of which were non-synonymous, distinguished outbreak from non-outbreak isolates. Lineage-specific markers indicated that recent partitions were driven by selective pressures associated with niche adaptation. Based on the results, an evolutionary model for STEC O104:H4 is proposed. Our analysis provides the evolutionary context at population level and describes the emergence of clones with novel properties, which is necessary for developing comprehensive approaches to early warning and control. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    No preview · Article · Dec 2014 · Clinical Microbiology and Infection

Publication Stats

7k Citations
848.66 Total Impact Points

Institutions

  • 2014-2015
    • Universitair Medisch Centrum Groningen
      • Department of Medical Microbiology
      Groningen, Groningen, Netherlands
  • 2006-2015
    • University of Groningen
      • Department of Medical Microbiology
      Groningen, Groningen, Netherlands
  • 2012
    • Universitetet i Tromsø
      Tromsø, Troms, Norway
  • 2005-2011
    • National Institute for Public Health and the Environment (RIVM)
      • • Epidemiology and Surveillance Unit (EPI)
      • • Centre for Infectious Disease Control (CIb)
      Utrecht, Utrecht, Netherlands
  • 1996-2005
    • University of Freiburg
      • Institute of Medical Biometry and Medical Informatics
      Freiburg, Baden-Württemberg, Germany
  • 1999-2004
    • University of Nottingham
      • • Centre for Sports Medicine
      • • Faculty of Medicine and Health Sciences
      Nottigham, England, United Kingdom
  • 2003
    • University of Bath
      • Department of Biology and Biochemistry
      Bath, England, United Kingdom